Abstract

OBJECTIVE There is a complex relationship between IGF-I, IGF binding proteins, growth hormone, and insulin. The IGF-I kinase receptor
activation assay (KIRA) is a novel method for measuring IGF-I bioactivity in human serum. We speculated that determination
of IGF-I bioactivity might broaden our understanding of the IGF-I system in subjects with the metabolic syndrome. The purpose
of our study was to investigate whether IGF-I bioactivity was related to insulin sensitivity and the metabolic syndrome.

RESEARCH DESIGN AND METHODS We conducted a cross-sectional study embedded in a random sample (1,036 elderly subjects) of a prospective population-based
cohort study. IGF-I bioactivity was determined by the IGF-I KIRA. Categories of glucose (in)tolerance were defined by the
2003 American Diabetes Association criteria. Insulin sensitivity was assessed by homeostasis model assessment. The Adult Treatment
Panel III definition of the metabolic syndrome was used.

RESULTS In subjects with normal fasting glucose and impaired fasting glucose, IGF-I bioactivity progressively increased with increasing
insulin resistance, peaked at fasting glucose levels just below 7.0 mmol/l, and dropped at higher glucose levels. Mean IGF-I
bioactivity peaked when three criteria of the metabolic syndrome were present and then declined significantly when five criteria
of the metabolic syndrome were present.

CONCLUSIONS We observed that IGF-I bioactivity was related to insulin sensitivity, insulin levels, and the metabolic syndrome. Our study
suggests that there exists an inverse U-shaped relationship between IGF-I bioactivity and number of components of the metabolic
syndrome. This observation contrasts with previous results reporting an inverse relationship between total IGF-I and components
of the metabolic syndrome.

Footnotes

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